2. PROTAC MAPK/ERK Pathway GPCR/G Protein
  3. PROTACs Ras
  4. ACBI-4

ACBI-4 is a selective GTP-loaded active state of KRAS (KRAS(on)) PROTAC degrader, with Kd values of 141 nM against KRASG12R. ACBI-4 forms a stable ternary complex with VHL, triggering ubiquitination and KRAS degradation via the ubiquitin-proteasome system. ACBI-4 induces antiproliferative effects in KRAS mutant-driven cancer cells. ACBI-4 can be used for the research of KRAS mutant-driven cancer.
(Pink: KRas G12R ligand (HY-162960); Blue: VHL ligand (HY-176917); Black: linker).

For research use only. We do not sell to patients.

ACBI-4

ACBI-4 Chemical Structure

CAS No. : 3097985-19-5

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Based on 1 publication(s) in Google Scholar

Other Forms of ACBI-4:

ACBI-4 Related Antibodies

Top Publications Citing Use of Products

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

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K-Ras H-Ras N-Ras Ras

  • Biological Activity

  • Purity & Documentation

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Description

ACBI-4 is a selective GTP-loaded active state of KRAS (KRAS(on)) PROTAC degrader, with Kd values of 141 nM against KRASG12R. ACBI-4 forms a stable ternary complex with VHL, triggering ubiquitination and KRAS degradation via the ubiquitin-proteasome system. ACBI-4 induces antiproliferative effects in KRAS mutant-driven cancer cells. ACBI-4 can be used for the research of KRAS mutant-driven cancer[1]. (Pink: KRas G12R ligand (HY-162960); Blue: VHL ligand (HY-176917); Black: linker).

IC50 & Target[1]

KRas G12R

141 nM (Kd)

In Vitro

ACBI-4 (0.01-10 μM) potently degrades endogenous KRASG12R in Cal-62 cells with a DC50 of 162 nM and 93% maximal degradation at 18 h, acting via a PROTAC-dependent mechanism involving VHL recruitment and proteasomal degradation[1].
ACBI-4 (0.1 nM-10 μM; 6 day) exerts a dose-dependent antiproliferative effect in KRASG12R-driven Cal-62 cells, with no activity in KRAS-independent A375 cells, demonstrating on-target efficacy[1].
ACBI-4 (0.02-1000 nM; 18 h) degrades all tested oncogenic KRAS mutants in transduced GP5d cells, with notably enhanced degradation of KRASG12R, KRASQ61K, KRASQ61L, and KRASQ61R compared to ACBI3 (HY-157228)[1].
ACBI-4 (0.01-10 μM; 18 h) degrades endogenous KRASG12R, KRASQ61K, KRASQ61L, and KRASG12D in their respective cancer cell lines in a dose-dependent manner[1].
ACBI-4 (0.1-10 μM) degrades HiBiT-tagged KRASG12R in Cal-62 cells at a faster rate than compound 1, with a maximum rate of ~0.3 min−1 at concentrations ≥1 μM[1].
ACBI-4 (1 μM; 6 h) selectively degrades KRAS in Cal-62 cells, with minimal degradation of closely related NRAS and HRAS at therapeutic-relevant concentrations, and modulates levels of MAPK pathway-related proteins[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ACBI-4 Related Antibodies

Cell Viability Assay[1]

Cell Line: Cal-62 (KRASG12R) cancer cells, KRAS-independent A375 cells
Concentration: 0.1 nM; 1 nM; 10 nM; 100 nM; 1 μM; 10 μM
Incubation Time: 6 day
Result: Induced a dose-dependent antiproliferative effect in Cal-62 cells.
Showed no antiproliferative activity in KRAS-independent A375 cells, confirming on-target activity.

Western Blot Analysis[1]

Cell Line: retrovirally transduced GP5d cells (multiple KRAS mutants)
Concentration: 0.02 nM; 0.15 nM; 0.46 nM; 1.4 nM; 4 nM; 12 nM; 37 nM; 111 nM; 333 nM; 1000 nM
Incubation Time: 18 h
Result: Degraded all tested oncogenic KRAS mutants, including KRASG12R, KRASQ61K, KRASQ61L, KRASQ61R, KRASG12D, KRASG12V, KRASG13D, KRASG13V, KRASQ61E, KRASA146P, KRASA146T, and KRASA146V.
Showed significantly improved degradation of KRASG12R, KRASQ61K, KRASQ61L, and KRASQ61R compared to ACBI3, with only KRASA146P showing similar degradation levels to ACBI3.

Western Blot Analysis[1]

Cell Line: Calu-6 (KRASQ61K), SW948 (KRASQ61L), KP-2 (KRASG12R), GP5d (KRASG12D)
Concentration: 0.01 μM; 0.03 μM; 0.1 μM; 0.3 μM; 1 μM; 10 μM
Incubation Time: 18 h
Result: Induced dose-dependent degradation of endogenous KRASQ61K in Calu-6 cells.
Induced dose-dependent degradation of endogenous KRASQ61L in SW948 cells, requiring higher concentrations for maximal effect.
Induced dose-dependent degradation of endogenous KRASG12R in KP-2 cells.
Induced dose-dependent degradation of endogenous KRASG12D in GP5d cells.
Molecular Weight

970.20

Formula

C50H63N15O4S
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

CC([C@H](N1N=NC2=C1CC[C@H](CCCN3C[C@@H](N(CCC3)C4=NC(C5=NOC([C@@]6(C7=C(CCC6)SC(N)=C7C#N)C)=N5)=CC=N4)C)C2)C(N8C[C@@H](C[C@H]8C(NCC9=CC=C%10C(N(N=C%10)C)=C9)=O)O)=O)C
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

-20°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

Solvent & Solubility
In Vitro: 

DMSO : 50 mg/mL (51.54 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.0307 mL 5.1536 mL 10.3072 mL
5 mM 0.2061 mL 1.0307 mL 2.0614 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.0307 mL 5.1536 mL 10.3072 mL 25.7679 mL
5 mM 0.2061 mL 1.0307 mL 2.0614 mL 5.1536 mL
10 mM 0.1031 mL 0.5154 mL 1.0307 mL 2.5768 mL
15 mM 0.0687 mL 0.3436 mL 0.6871 mL 1.7179 mL
20 mM 0.0515 mL 0.2577 mL 0.5154 mL 1.2884 mL
25 mM 0.0412 mL 0.2061 mL 0.4123 mL 1.0307 mL
30 mM 0.0344 mL 0.1718 mL 0.3436 mL 0.8589 mL
40 mM 0.0258 mL 0.1288 mL 0.2577 mL 0.6442 mL
50 mM 0.0206 mL 0.1031 mL 0.2061 mL 0.5154 mL
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ACBI-4 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

ACBI-43097985-19-5ACBI4ACBI 4PROTACsRasKRASG12RKRASG12DVHLGTP-bound KRASVCBMAPK pathwayCal-62 cellsGP5d cellsA375 cellsubiquitin-proteasome systemInhibitorinhibitorinhibit

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